How important is it for multiple myeloma (MM) patients to know if they have double-hit MM?

MM patients who have two different chromosomal abnormalities (an example would be chromosome 1q amplification and chromosome 17p deletion) have double-hit MM. Double-hit MM is considered to be a high-risk disease feature which means these patients have a poor prognosis despite receiving current standard of care therapies. MM clinicians don’t expect their patients to be genomic experts and you don’t have to worry about exactly which chromosomal abnormalities you may or may not have! Rather, it is more important to be an active and engaged patient with your MM specialist and have an upfront conversation with him or her about whether your disease is easy to treat, hard to treat, or somewhere in between. Equally important is to know which clinical trials are available in your area.

Can a MM patient convert from high-risk to standard-risk disease after treatment or vice versa?

A patient cannot convert from having high-risk to standard-risk MM following treatment. For example, a newly diagnosed patient who has a chromosome 17p deletion and is treated with an induction regimen followed by an autologous stem cell transplant and achieved a complete response will show that the chromosomal abnormality went away, but that is only because the myeloma cells are gone; they were eliminated by the treatment. However, when the myeloma becomes active again and the patient relapses, that chromosomal abnormality will be seen again in the bone marrow biopsy test results.

The opposite is true: patients with standard-risk MM may convert to high-risk MM. High-risk chromosomal abnormalities may appear after a patient relapses. Therefore, it is important to repeat a bone marrow biopsy after relapse to determine if the MM has changed and become more aggressive.

With the approval of three new bispecific antibodies, what are the implications of using these for high-risk MM patients?

The MM therapeutic field has been rapidly advancing and it is truly an exciting and hopeful time for MM patients! Tecvayli (teclistamab) was approved for use in relapsed/refractory MM patients in October 2022 and two more bispecific antibodies were approved in August 2023 within a week: Talvey (talquetamab) and Elrexfio (elranatamab). Two of the bispecifics (Tecvayli and Elrexfio) target BCMA on myeloma cells (the same target for the two approved CAR T cell therapies Abecma and Carvykti) and one (Talvey) targets GPRC5D.

All bispecific antibodies are very effective in patients with relapsed/refractory MM as they can induce a response in over 60% of patients who have received many prior treatments. The key issue when treating relapsed/refractory patients is that clinicians are unclear how to sequence all the drugs—bispecific antibodies and CAR T cells—that are available to patients with relapsed/refractory MM. The bispecific antibodies have not been studied in patients who have relapsed after receiving CAR T cell therapy. However, as the bispecific antibodies are being used in the clinic, real-world experience is being gathered and many patients are being treated with bispecific antibodies after CAR T cell therapy. And the good news, is that data suggests that patients are responding.

Ultimately, the bispecific antibodies are one of several options for patients and, like all other drugs, if they are effective in the relapsed/refractory setting, they  are likely to be effective earlier in the disease course. Many clinical studies are underway in patients with earlier relapse (that is, only 1 to 3 prior lines of therapy) and in newly diagnosed disease and the MM community looks forward to seeing the results!